Department of Radiology and National Clinical Research Center for Geriatrics, Huaxi MR Research Center, West China Hospital of Sichuan University, Chengdu, China.
Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
Schizophr Bull. 2023 Mar 15;49(2):417-427. doi: 10.1093/schbul/sbac121.
Cerebellar functional dysconnectivity has long been implicated in schizophrenia. However, the detailed dysconnectivity pattern and its underlying biological mechanisms have not been well-charted. This study aimed to conduct an in-depth characterization of cerebellar dysconnectivity maps in early schizophrenia.
Resting-state fMRI data were processed from 196 drug-naïve patients with first-episode schizophrenia and 167 demographically matched healthy controls. The cerebellum was parcellated into nine functional systems based on a state-of-the-art atlas, and seed-based connectivity for each cerebellar system was examined. The observed connectivity alterations were further associated with schizophrenia risk gene expressions using data from the Allen Human Brain Atlas.
Overall, we observed significantly increased cerebellar connectivity with the sensorimotor cortex, default-mode regions, ventral part of visual cortex, insula, and striatum. In contrast, decreased connectivity was shown chiefly within the cerebellum, and between the cerebellum and the lateral prefrontal cortex, temporal lobe, and dorsal visual areas. Such dysconnectivity pattern was statistically similar across seeds, with no significant group by seed interactions identified. Moreover, connectivity strengths of hypoconnected but not hyperconnected regions were significantly correlated with schizophrenia risk gene expressions, suggesting potential genetic underpinnings for the observed hypoconnectivity.
These findings suggest a common bidirectional dysconnectivity pattern across different cerebellar subsystems, and imply that such bidirectional alterations may relate to different biological mechanisms.
小脑功能连接障碍长期以来一直被认为与精神分裂症有关。然而，详细的连接障碍模式及其潜在的生物学机制尚未得到很好的描述。本研究旨在深入描述早期精神分裂症患者小脑的连接障碍图谱。
对 196 名未经药物治疗的首发精神分裂症患者和 167 名年龄匹配的健康对照者的静息态 fMRI 数据进行了处理。基于最新的图谱，将小脑分为九个功能系统，并检查了每个小脑系统的种子连接。使用来自 Allen 人类大脑图谱的数据，进一步将观察到的连接变化与精神分裂症风险基因表达相关联。
总的来说，我们观察到小脑与感觉运动皮层、默认模式区域、视觉皮层腹侧部分、岛叶和纹状体的连接显著增加。相比之下，小脑内部和小脑与外侧前额叶皮层、颞叶和背侧视觉区域之间的连接减少。这种连接障碍模式在各个种子中都具有统计学上的相似性，没有发现组间种子相互作用的显著差异。此外，连接较弱而非连接较强的区域的连接强度与精神分裂症风险基因表达显著相关，这表明观察到的连接减弱可能有潜在的遗传基础。
这些发现表明不同小脑子系统之间存在共同的双向连接障碍模式，并暗示这种双向改变可能与不同的生物学机制有关。
